Monoclonal antibodies are routinely used as therapeutics in a number of disease settings and have thus also been explored as potential treatment for human immunodeficiency virus (HIV)-1 infection. Antibodies targeting viral antigens, and those directed to the cellular receptors, have been considered for use in prevention and therapy. For virus-targeted antibodies, attention has focused primarily on their neutralizing activity, but such antibodies also have the potential to exert antiviral effects via effector functions, such as antibody-dependent cellular cytotoxicity (ADCC), opsonization, or complement activation. Anti-cell antibodies act through occlusion or down-modulation of the viral receptors with notable impact in vivo, as recent trials have shown. This review summarizes the diverse specificities and modes of action of therapeutic antibodies against HIV-1 infection. Successes, challenges, and future opportunities of harnessing antibodies for therapy of HIV-1 infection are discussed.